Treatment of acute lung injury by targeting MG53-mediated cell membrane repair

Nat Commun. 2014 Jul 18;5:4387. doi: 10.1038/ncomms5387.

Abstract

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischaemia-reperfusion and overventilation-induced injury to the lung when compared with wild-type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / genetics
  • Acute Lung Injury / pathology*
  • Animals
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / pharmacology*
  • Cell Hypoxia / drug effects
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Lung / pathology
  • Male
  • Membrane Proteins
  • Mice, Knockout
  • Molecular Targeted Therapy / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / pathology
  • Respiration, Artificial / adverse effects
  • Tripartite Motif Proteins

Substances

  • Carrier Proteins
  • MG53 protein, mouse
  • Membrane Proteins
  • Recombinant Proteins
  • TRIM72 protein, human
  • Tripartite Motif Proteins